Dengue virus (DENV) is the most important arboviral cause of morbidity and mortality throughout the world. There are currently 2.5 billion people living in dengue endemic regions with roughly 100 million annual cases of dengue fever and hundreds of thousands of cases of dengue hemorrhagic fever and dengue shock syndrome (Gubler, Clin. Microbiol. Rev. 11:480-496, 1998). No vaccines are currently commercially available against any of the four DENV serotypes (DENV 1-4) largely because vaccine production is hampered by the fact that neutralizing antibodies to one serotype do not effectively neutralize the remaining DENV serotypes (Halstead and O'Rourke, J. Exp. Med. 146:201-217, 1977). In fact, low levels of these antibodies may actually increase the risk for more severe disease during secondary infection due to a phenomenon known as antibody mediated enhancement, which occurs when antibodies against one DENV serotype bind in a non-neutralizing manner to DENV particles of another serotype. This binding allows increased infection of Fc receptor-bearing cells, such as macrophages, which can change the infection profile of the virus or cause a release of chemokines leading to dengue hemorrhagic fever or dengue shock syndrome (Halstead and O'Rourke, J. Exp. Med. 146:201-217, 1977).
West Nile virus (WNV) is a member of the Japanese encephalitis serocomplex in the genus Flavivirus, family Flaviviridae. Until the mid-1990s, WNV caused sporadic outbreaks of illness in Africa, the Middle East, and Western Asia. However, since 1996, WN encephalitis has been reported more frequently in Europe, the Middle East, northern and western Africa, and Russia. WNV emerged in the western hemisphere in 1999 and has become the leading cause of arboviral encephalitis in humans and equines in North America. There are two lineages of WNV. Lineage 1, of which the NY99 strain is a member, is the more virulent strain and is the predominant strain infecting humans and horses (Jordan et al., Viral Immunol. 13:435-446, 2000). There is currently no approved vaccine for WNV to protect at-risk human populations from WN illness.